Neuroimaging and Gene Expression Correlations in Psychiatric Disorders

Psychiatric disorders arise from complex interactions between genetic factors and brain network organisation. Advances in neuroimaging and transcriptomics have enabled the integration of structural and functional brain maps with spatially resolved gene expression data. High-resolution magnetic resonance imaging (MRI) captures cortical morphology and connectivity patterns, while large-scale gene atlases provide regional transcriptional profiles. By correlating imaging phenotypes with gene co-expression, researchers have identified molecular signatures that underlie regional vulnerability to illness. Structural covariance analyses and morphometric similarity networks reveal how inter-regional anatomical similarities track co-expressed genes enriched for neuronal and glial markers. Resting-state functional measurements further uncover distinct transcriptomic correlates of functional dysregulation. Together, these approaches bridge macroscale brain alterations with cell type-specific transcriptional pathways, offering mechanistic insight into the development of major depressive disorder, schizophrenia spectrum illnesses, autism and other conditions. The integration of imaging and gene expression data promises to refine our understanding of disease heterogeneity, suggest novel biomarkers and inform targeted therapeutic strategies.

Research from Nature Portfolio

Recent studies have refined methods for linking cortical organisation to gene expression. A novel morphometric inverse divergence framework leverages multivariate MRI features to construct cortical similarity networks that align more closely with gene co-expression patterns than traditional approaches. This technique demonstrates enhanced sensitivity to developmental changes and heritable network traits, providing a biologically validated tool for future psychiatric investigations. A comprehensive atlas of neurotransmitter receptors, assembled from positron emission tomography data, corresponds with structural connectivity and resting-state functional patterns. Receptor distributions reveal spatial gradients separating extrinsic sensory-motor processes from intrinsic cognitive functions and correlate with cortical abnormality maps across multiple disorders. Investigations of major depressive disorder using morphometric similarity networks have identified a replicable pattern of cortical structural differences whose regional distribution is spatially coupled to cell type-specific transcriptional signatures, implicating microglial and neuronal pathways in disease-related structural alterations.

Neuroimaging and Gene Expression Correlations in Psychiatric Disorders publication trend

The graph below shows the total number of articles in neuroimaging and gene expression correlations in psychiatric disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Gene expression: The process by which information from a gene is used to synthesise functional gene products, reflecting regional transcriptional activity.

Transcriptomics: Large-scale study of RNA transcripts to map spatial patterns of gene expression across cortical regions.

Morphometric similarity network (MSN): A graph-based model in which edges represent multivariate similarity of anatomical features between brain regions.

Connectome: Comprehensive map of structural or functional neural connections forming the brain’s network architecture.

Hub vulnerability: A model proposing that network hubs, or highly connected regions, are more susceptible to disease-related alterations.

Epicentre mapping: Identification of regions whose connectivity profiles most closely resemble spatial patterns of pathology in a disorder.

References

1. Structural covariance networks are coupled to expression of genes enriched in supragranular layers of the human cortex. NeuroImage (2017).
2. Morphometric Similarity Networks Detect Microscale Cortical Organization and Predict Inter-Individual Cognitive Variation. Neuron (2017).
3. Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes. Proceedings of the National Academy of Sciences of the United States of America (2019).
4. Robust estimation of cortical similarity networks from brain MRI. Nature Neuroscience (2023).
5. Mapping neurotransmitter systems to the structural and functional organization of the human neocortex. Nature Neuroscience (2022).
6. Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures. Nature Communications (2021).
7. Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study. Molecular Psychiatry (2024).
8. Gene Expression has Distinct Associations with Brain Structure and Function in Major Depressive Disorder. Advanced Science (2023).